CA2966620A1 - Aadc polynucleotides for the treatment of parkinson's disease - Google Patents
Aadc polynucleotides for the treatment of parkinson's disease Download PDFInfo
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- CA2966620A1 CA2966620A1 CA2966620A CA2966620A CA2966620A1 CA 2966620 A1 CA2966620 A1 CA 2966620A1 CA 2966620 A CA2966620 A CA 2966620A CA 2966620 A CA2966620 A CA 2966620A CA 2966620 A1 CA2966620 A1 CA 2966620A1
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US62/243,537 | 2015-10-19 | ||
PCT/US2015/059201 WO2016073693A2 (en) | 2014-11-05 | 2015-11-05 | Aadc polynucleotides for the treatment of parkinson's disease |
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JP6401871B2 (ja) | 2014-11-05 | 2018-10-10 | ボイジャー セラピューティクス インコーポレイテッドVoyager Therapeutics,Inc. | パーキンソン病の治療のためのaadcポリヌクレオチド |
RU2749882C2 (ru) | 2014-11-14 | 2021-06-18 | Вояджер Терапьютикс, Инк. | Модулирующие полинуклеотиды |
EP3632923A1 (en) * | 2015-01-16 | 2020-04-08 | Voyager Therapeutics, Inc. | Central nervous system targeting polynucleotides |
AU2016362477A1 (en) | 2015-12-02 | 2018-06-14 | Voyager Therapeutics, Inc. | Assays for the detection of AAV neutralizing antibodies |
JP7220080B2 (ja) | 2016-05-18 | 2023-02-09 | ボイジャー セラピューティクス インコーポレイテッド | ハンチントン病治療組成物及び方法 |
JP7066635B2 (ja) | 2016-05-18 | 2022-05-13 | ボイジャー セラピューティクス インコーポレイテッド | 調節性ポリヌクレオチド |
US11298041B2 (en) | 2016-08-30 | 2022-04-12 | The Regents Of The University Of California | Methods for biomedical targeting and delivery and devices and systems for practicing the same |
US11111271B2 (en) | 2016-09-28 | 2021-09-07 | Cohbar, Inc. | Therapeutic peptides |
US11117930B2 (en) | 2017-02-23 | 2021-09-14 | Adrx, Inc. | Peptide inhibitors of transcription factor aggregation |
AU2018234918B2 (en) * | 2017-03-17 | 2023-11-02 | Adverum Biotechnologies, Inc. | Compositions and methods for enhanced gene expression |
WO2018191450A2 (en) | 2017-04-14 | 2018-10-18 | National Taiwan University Hospital | Gene therapy for aadc deficiency |
WO2018204803A1 (en) * | 2017-05-05 | 2018-11-08 | Voyager Therapeutics, Inc. | Compositions and methods of treating huntington's disease |
WO2018226992A1 (en) | 2017-06-07 | 2018-12-13 | Adrx, Inc. | Tau aggregation inhibitors |
JOP20190269A1 (ar) * | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
US11497576B2 (en) | 2017-07-17 | 2022-11-15 | Voyager Therapeutics, Inc. | Trajectory array guide system |
CN112501208A (zh) * | 2017-10-03 | 2021-03-16 | 普利维尔治疗公司 | 用于溶酶体障碍的基因疗法 |
JP2021521852A (ja) * | 2018-04-27 | 2021-08-30 | ボイジャー セラピューティクス インコーポレイテッドVoyager Therapeutics,Inc. | Aadcウイルスベクターの効力を測定する方法 |
AU2019268330A1 (en) | 2018-05-15 | 2020-11-26 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of Parkinson's disease |
WO2019222441A1 (en) * | 2018-05-16 | 2019-11-21 | Voyager Therapeutics, Inc. | Aav serotypes for brain specific payload delivery |
US12060567B2 (en) | 2018-06-13 | 2024-08-13 | Voyager Therapeutics, Inc. | Engineered untranslated regions (UTR) for AAV production |
CN114908099B (zh) * | 2018-06-28 | 2024-07-02 | 北京锦篮基因科技有限公司 | 携带设计smn1基因表达框的重组腺相关病毒及应用 |
MX2021000810A (es) | 2018-07-24 | 2021-04-28 | Voyager Therapeutics Inc | Sistemas y metodos para producir formulaciones de terapia genetica. |
KR20210068068A (ko) * | 2018-09-28 | 2021-06-08 | 보이저 테라퓨틱스, 인크. | 조작된 프로모터를 갖는 프라탁신 발현 구축물 및 그의 사용 방법 |
TW202035689A (zh) | 2018-10-04 | 2020-10-01 | 美商航海家醫療公司 | 測量病毒載體粒子的效價及強度之方法 |
TW202028458A (zh) | 2018-10-05 | 2020-08-01 | 美商航海家醫療公司 | 編碼腺相關病毒(aav)生產蛋白之經基因工程化核酸構築體 |
CN113166781A (zh) | 2018-10-15 | 2021-07-23 | 沃雅戈治疗公司 | 在杆状病毒/Sf9系统中大规模生产rAAV的表达载体 |
MX2021008542A (es) | 2019-01-18 | 2021-11-12 | Voyager Therapeutics Inc | Métodos y sistemas para la producción de partículas de aav. |
KR20210121132A (ko) | 2019-01-28 | 2021-10-07 | 코바, 인크. | 치료용 펩티드 |
EP3917566A4 (en) | 2019-01-31 | 2022-10-26 | Oregon Health & Science University | METHODS OF USING TRANSCRIPTION-DEPENDENT DIRECTED EVOLUTION OF AAV CAPSIDS |
CA3128875A1 (en) | 2019-02-04 | 2020-08-13 | Freeline Therapeutics Limited | Polynucleotides |
CN109971729B (zh) * | 2019-04-19 | 2021-07-16 | 上海信致医药科技有限公司 | 一种酶组合物 |
US20220243225A1 (en) | 2019-04-29 | 2022-08-04 | Voyager Therapeutics, Inc. | SYSTEMS AND METHODS FOR PRODUCING BACULOVIRAL INFECTED INSECT CELLS (BIICs) IN BIOREACTORS |
US20220290182A1 (en) | 2019-08-09 | 2022-09-15 | Voyager Therapeutics, Inc. | Cell culture medium for use in producing gene therapy products in bioreactors |
WO2021041485A1 (en) | 2019-08-26 | 2021-03-04 | Voyager Therapeutics, Inc. | Controlled expression of viral proteins |
CN115135347A (zh) * | 2019-12-12 | 2022-09-30 | 梅里特斯英国第二有限公司 | 治疗帕金森病的方法 |
US20230242939A1 (en) * | 2020-01-29 | 2023-08-03 | Voyager Therapeutics, Inc. | Methods and systems for producing aav particles |
RU2742837C1 (ru) * | 2020-06-02 | 2021-02-11 | Общество С Ограниченной Ответственностью "Анабион" | Кодон-оптимизированная нуклеиновая кислота, которая кодирует белок SMN1, и ее применение |
EP4192514A1 (en) | 2020-08-06 | 2023-06-14 | Voyager Therapeutics, Inc. | Cell culture medium for use in producing gene therapy products in bioreactors |
EP3982378A1 (en) | 2020-10-09 | 2022-04-13 | Koninklijke Philips N.V. | Cryogen-free superconducting magnet system |
WO2022187548A1 (en) | 2021-03-03 | 2022-09-09 | Voyager Therapeutics, Inc. | Controlled expression of viral proteins |
US20240141377A1 (en) | 2021-03-03 | 2024-05-02 | Voyager Therapeutics, Inc. | Controlled expression of viral proteins |
KR20220128589A (ko) * | 2021-03-12 | 2022-09-21 | 코오롱생명과학 주식회사 | 퇴행성 뇌질환 예방 또는 치료용 조성물 |
WO2022212271A1 (en) * | 2021-03-29 | 2022-10-06 | Sanford Health | Methods and compositions for treating lysosomal storage disorders |
WO2023279078A1 (en) * | 2021-07-01 | 2023-01-05 | Northwestern University | Enhanced expression of an aromatic amino acid decarboxylase (aadc) in the substantia nigra for the treatment of parkinson's disease |
EP4409010A1 (en) | 2021-10-02 | 2024-08-07 | The Trustees of The University of Pennsylvania | Novel aav capsids and compositions containing same |
AU2022379918A1 (en) | 2021-11-02 | 2024-04-18 | Voyager Therapeutics, Inc. | Aav capsid variants and uses thereof |
CN118525098A (zh) * | 2021-11-29 | 2024-08-20 | 上海瑞宏迪医药有限公司 | Aadc、gdnf多核苷酸及其用于治疗帕金森病 |
WO2023202637A1 (en) * | 2022-04-19 | 2023-10-26 | Shanghai Vitalgen Biopharma Co., Ltd. | Recombinant aav vectors for treating neurodegenerative disorders |
WO2024054983A1 (en) | 2022-09-08 | 2024-03-14 | Voyager Therapeutics, Inc. | Controlled expression of viral proteins |
CN118252953A (zh) * | 2022-12-26 | 2024-06-28 | 科辉智药(深圳)新药研究中心有限公司 | 一种用于神经退行性疾病治疗的基因序列构建体及其应用 |
WO2025060451A1 (zh) * | 2023-09-18 | 2025-03-27 | 上海金珂博生物技术有限公司 | 经修饰的腺相关病毒载体及其在治疗神经疾病中的用途 |
Family Cites Families (457)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2640638B1 (fr) | 1988-12-20 | 1991-02-15 | Commissariat Energie Atomique | Bioreacteur et dispositif pour la culture de cellules animales |
AU7906691A (en) | 1990-05-23 | 1991-12-10 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | Adeno-associated virus (aav)-based eucaryotic vectors |
US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
GB9027917D0 (en) * | 1990-12-21 | 1991-02-13 | Ici Plc | Expression systems |
US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
US6268213B1 (en) | 1992-06-03 | 2001-07-31 | Richard Jude Samulski | Adeno-associated virus vector and cis-acting regulatory and promoter elements capable of expressing at least one gene and method of using same for gene therapy |
US5693531A (en) | 1993-11-24 | 1997-12-02 | The United States Of America As Represented By The Department Of Health And Human Services | Vector systems for the generation of adeno-associated virus particles |
DE69535703T2 (de) | 1994-04-13 | 2009-02-19 | The Rockefeller University | AAV-vermittelte Zufuhr von DNA an Zellen des Nervensystems |
US20020159979A1 (en) | 1994-06-06 | 2002-10-31 | Children's Hospital, Inc. | Adeno-associated virus materials and methods |
US5658785A (en) | 1994-06-06 | 1997-08-19 | Children's Hospital, Inc. | Adeno-associated virus materials and methods |
US6204059B1 (en) | 1994-06-30 | 2001-03-20 | University Of Pittsburgh | AAV capsid vehicles for molecular transfer |
US5856152A (en) | 1994-10-28 | 1999-01-05 | The Trustees Of The University Of Pennsylvania | Hybrid adenovirus-AAV vector and methods of use therefor |
US5625048A (en) | 1994-11-10 | 1997-04-29 | The Regents Of The University Of California | Modified green fluorescent proteins |
US5652224A (en) | 1995-02-24 | 1997-07-29 | The Trustees Of The University Of Pennsylvania | Methods and compositions for gene therapy for the treatment of defects in lipoprotein metabolism |
US5741657A (en) | 1995-03-20 | 1998-04-21 | The Regents Of The University Of California | Fluorogenic substrates for β-lactamase and methods of use |
US6281010B1 (en) | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
US5756283A (en) | 1995-06-05 | 1998-05-26 | The Trustees Of The University Of Pennsylvania | Method for improved production of recombinant adeno-associated viruses for gene therapy |
US5741683A (en) | 1995-06-07 | 1998-04-21 | The Research Foundation Of State University Of New York | In vitro packaging of adeno-associated virus DNA |
US5688676A (en) | 1995-06-07 | 1997-11-18 | Research Foundation Of State University Of New York | In vitro packaging of adeno-associated virus DNA |
US6197293B1 (en) | 1997-03-03 | 2001-03-06 | Calydon, Inc. | Adenovirus vectors specific for cells expressing androgen receptor and methods of use thereof |
US6676935B2 (en) | 1995-06-27 | 2004-01-13 | Cell Genesys, Inc. | Tissue specific adenoviral vectors |
WO1997008298A1 (en) | 1995-08-30 | 1997-03-06 | Genzyme Corporation | Chromatographic purification of adenovirus and aav |
US6265389B1 (en) | 1995-08-31 | 2001-07-24 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of oligonucleotides |
US5858351A (en) | 1996-01-18 | 1999-01-12 | Avigen, Inc. | Methods for delivering DNA to muscle cells using recombinant adeno-associated virus vectors |
US5846528A (en) | 1996-01-18 | 1998-12-08 | Avigen, Inc. | Treating anemia using recombinant adeno-associated virus virions comprising an EPO DNA sequence |
US5962313A (en) | 1996-01-18 | 1999-10-05 | Avigen, Inc. | Adeno-associated virus vectors comprising a gene encoding a lyosomal enzyme |
US5952221A (en) | 1996-03-06 | 1999-09-14 | Avigen, Inc. | Adeno-associated virus vectors comprising a first and second nucleic acid sequence |
US7026468B2 (en) | 1996-07-19 | 2006-04-11 | Valentis, Inc. | Process and equipment for plasmid purification |
AU4255397A (en) | 1996-09-06 | 1998-03-26 | Trustees Of The University Of Pennsylvania, The | Chimpanzee adenovirus vectors |
US20020037867A1 (en) | 1999-02-26 | 2002-03-28 | James M. Wilson | Method for recombinant adeno-associated virus-directed gene therapy |
ATE380037T1 (de) | 1996-09-06 | 2007-12-15 | Univ Pennsylvania | Verfaheren zur durch rekombinante adeno- assoziierte virus-gerichtete gentherapie |
CA2264499A1 (en) | 1996-09-06 | 1998-03-12 | The Trustees Of The University Of Pennsylvania | Methods using cre-lox for production of recombinant adeno-associated viruses |
JP2001500015A (ja) | 1996-09-06 | 2001-01-09 | トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | T7ポリメラーゼを利用する組換えアデノ随伴ウイルスの誘導可能な製造方法 |
US5866552A (en) | 1996-09-06 | 1999-02-02 | The Trustees Of The University Of Pennsylvania | Method for expressing a gene in the absence of an immune response |
CA2265460A1 (en) | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, Represented By The Secre Tary, Department Of Health And Human Services | Aav4 vector and uses thereof |
US7732129B1 (en) | 1998-12-01 | 2010-06-08 | Crucell Holland B.V. | Method for the production and purification of adenoviral vectors |
DE69737107T2 (de) | 1996-11-20 | 2007-07-12 | Introgen Therapeutics Inc., Austin | Ein verbessertes verfahren zur produktion und reinigung von adenoviralen vektoren |
US6541258B2 (en) | 1996-12-18 | 2003-04-01 | Targeted Genetics Corporation | AAV split-packaging genes and cell lines comprising such genes for use in the production of recombinant AAV vectors |
US6156303A (en) | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
US6710036B2 (en) | 1997-07-25 | 2004-03-23 | Avigen, Inc. | Induction of immune response to antigens expressed by recombinant adeno-associated virus |
US6251677B1 (en) | 1997-08-25 | 2001-06-26 | The Trustees Of The University Of Pennsylvania | Hybrid adenovirus-AAV virus and methods of use thereof |
US6566118B1 (en) | 1997-09-05 | 2003-05-20 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
US6989264B2 (en) | 1997-09-05 | 2006-01-24 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
WO1999015677A1 (en) | 1997-09-19 | 1999-04-01 | The Trustees Of The University Of Pennsylvania | Method for gene transfer using bcl2 and compositions useful therein |
EP1015619A1 (en) | 1997-09-19 | 2000-07-05 | The Trustees Of The University Of Pennsylvania | Methods and cell line useful for production of recombinant adeno-associated viruses |
AU9319198A (en) | 1997-09-19 | 1999-04-05 | Trustees Of The University Of Pennsylvania, The | Methods and vector constructs useful for production of recombinant aav |
US6642051B1 (en) | 1997-10-21 | 2003-11-04 | Targeted Genetics Corporation | Amplifiable adeno-associated virus(AAV) packaging cassettes for the production of recombinant AAV vectors |
IT1297074B1 (it) | 1997-11-21 | 1999-08-03 | Angeletti P Ist Richerche Bio | Forme ormone-dipendenti delle proteine rep del virus adeno-associato (aav-2), sequenze di dna codificanti per esse, vettori che le |
JP2001526900A (ja) | 1997-12-23 | 2001-12-25 | イントロヘーネ ベスローテン フェンノートシャップ | 標的細胞の染色体dnaへの外来遺伝子情報の組み込みに有用な、アデノ随伴ウイルスおよびアデノウイルスのキメラ組換えウイルス |
US6410300B1 (en) | 1998-01-12 | 2002-06-25 | The University Of North Carolina At Chapel Hill | Methods and formulations for mediating adeno-associated virus (AAV) attachment and infection and methods for purifying AAV |
WO1999043360A1 (en) | 1998-02-26 | 1999-09-02 | The Trustees Of The University Of Pennsylvania | Stable protection from dystrophic sarcolemmal degeneration and restoration of the sarcoglycan complex |
US6953690B1 (en) | 1998-03-20 | 2005-10-11 | The Trustees Of The University Of Pennsylvania | Compositions and methods for helper-free production of recombinant adeno-associated viruses |
US6521426B1 (en) | 1998-04-08 | 2003-02-18 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Preparation of recombinant adenovirus carrying a rep gene of adeno-associated virus |
FR2778413B1 (fr) | 1998-05-07 | 2000-08-04 | Immunotech Sa | Nouveaux reactifs et methode de lyse des erythrocytes |
WO1999058700A1 (en) | 1998-05-11 | 1999-11-18 | Ariad Gene Therapeutics, Inc. | Multiviral compositions and uses thereof |
US6436392B1 (en) | 1998-05-20 | 2002-08-20 | University Of Iowa Research Foundation | Adeno-associated virus vectors |
EP1849872A1 (en) | 1998-05-20 | 2007-10-31 | University Of Iowa Research Foundation | Adeno-associated virus vectors and uses thereof |
US6146874A (en) | 1998-05-27 | 2000-11-14 | University Of Florida | Method of preparing recombinant adeno-associated virus compositions |
JP2002516295A (ja) * | 1998-05-27 | 2002-06-04 | アビジェン, インコーポレイテッド | Aavベクターの対流増加送達 |
AU4185699A (en) | 1998-05-27 | 1999-12-13 | Avigen, Inc. | Adeno-associated viral vector-mediated expression of factor viii activity |
EP1621626B1 (en) * | 1998-05-27 | 2009-07-08 | Genzyme Corporation | AAV Vectors for the manufacture of medicaments for convection enhanced delivery |
US6984517B1 (en) | 1998-05-28 | 2006-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | AAV5 vector and uses thereof |
ATE402254T1 (de) | 1998-05-28 | 2008-08-15 | Us Gov Health & Human Serv | Aav5 vektoren und deren verwendung |
GB2338236B (en) | 1998-06-13 | 2003-04-09 | Aea Technology Plc | Microbiological cell processing |
US6900049B2 (en) | 1998-09-10 | 2005-05-31 | Cell Genesys, Inc. | Adenovirus vectors containing cell status-specific response elements and methods of use thereof |
US6416992B1 (en) | 1998-10-13 | 2002-07-09 | Avigen, Inc. | Compositions and methods for producing recombinant adeno-associated virus |
US6200560B1 (en) | 1998-10-20 | 2001-03-13 | Avigen, Inc. | Adeno-associated virus vectors for expression of factor VIII by target cells |
US6221349B1 (en) | 1998-10-20 | 2001-04-24 | Avigen, Inc. | Adeno-associated vectors for expression of factor VIII by target cells |
MXPA01004169A (es) | 1998-10-27 | 2002-06-04 | Crucell Holland Bv | Produccion mejorada de vector de virus adenoasociados. |
US6759237B1 (en) | 1998-11-05 | 2004-07-06 | The Trustees Of The University Of Pennsylvania | Adeno-associated virus serotype 1 nucleic acid sequences, vectors and host cells containing same |
US6689600B1 (en) | 1998-11-16 | 2004-02-10 | Introgen Therapeutics, Inc. | Formulation of adenovirus for gene therapy |
US6759050B1 (en) | 1998-12-03 | 2004-07-06 | Avigen, Inc. | Excipients for use in adeno-associated virus pharmaceutical formulations, and pharmaceutical formulations made therewith |
US6225113B1 (en) | 1998-12-04 | 2001-05-01 | Genvec, Inc. | Use of trans-activation and cis-activation to modulate the persistence of expression of a transgene in an at least E4-deficient adenovirus |
US6387368B1 (en) | 1999-02-08 | 2002-05-14 | The Trustees Of The University Of Pennsylvania | Hybrid adenovirus-AAV virus and methods of use thereof |
DE19905501B4 (de) | 1999-02-10 | 2005-05-19 | MediGene AG, Gesellschaft für molekularbiologische Kardiologie und Onkologie | Verfahren zur Herstellung eines rekombinanten Adeno-assoziierten Virus, geeignete Mittel hierzu sowie Verwendung zur Herstellung eines Arzneimittels |
US6509150B1 (en) | 1999-03-05 | 2003-01-21 | Universite De Nantes | Compositions and methods for recombinant Adeno-Associated Virus production |
JP4693244B2 (ja) | 1999-03-18 | 2011-06-01 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 組換えアデノ随伴ウイルスのヘルパー無しの生産のための組成物および方法 |
US6258595B1 (en) | 1999-03-18 | 2001-07-10 | The Trustees Of The University Of Pennsylvania | Compositions and methods for helper-free production of recombinant adeno-associated viruses |
AU4807400A (en) | 1999-04-30 | 2000-11-17 | University Of Florida | Adeno-associated virus-delivered ribozyme compositions and methods of use |
JP2003501067A (ja) | 1999-06-02 | 2003-01-14 | トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | ヘルパーウイルスを要求する組み換えウイルス産生のために有用な組成物及び方法 |
WO2001014539A2 (en) | 1999-08-20 | 2001-03-01 | Johns Hopkins University School Of Medicine | Methods and compositions for the construction and use of fusion libraries |
CA2384814A1 (en) | 1999-09-29 | 2001-04-05 | The Trustees Of The University Of Pennsylvania | Methods for rapid peg-modification of viral vectors, compositions for enhanced gene transduction, compositions with enhanced physical stability, and uses therefor |
US6365394B1 (en) | 1999-09-29 | 2002-04-02 | The Trustees Of The University Of Pennsylvania | Cell lines and constructs useful in production of E1-deleted adenoviruses in absence of replication competent adenovirus |
US7241447B1 (en) | 1999-10-07 | 2007-07-10 | University Of Iowa Research Foundation | Adeno-associated virus vectors and uses thereof |
WO2001025465A1 (en) | 1999-10-07 | 2001-04-12 | University Of Iowa Research Foundation | Adeno-associated viruses and uses thereof |
WO2001032711A2 (en) | 1999-10-21 | 2001-05-10 | Board Of Trustees Of The University Of Arkansas | Adeno-associated virus aav rep78 major regulatory protein, mutants thereof and uses thereof |
WO2001036623A2 (en) | 1999-11-05 | 2001-05-25 | Avigen, Inc. | Ecdysone-inducible adeno-associated virus expression vectors |
US6582692B1 (en) | 1999-11-17 | 2003-06-24 | Avigen, Inc. | Recombinant adeno-associated virus virions for the treatment of lysosomal disorders |
EP1240345A2 (en) | 1999-12-10 | 2002-09-18 | Ariad Gene Therapeutics, Inc. | Methods for expression of genes in primates |
US20020045264A1 (en) | 2000-03-14 | 2002-04-18 | During Matthew J. | Production of chimeric capsid vectors |
US7638120B2 (en) | 2000-03-14 | 2009-12-29 | Thomas Jefferson University | High transgene expression of a pseudotyped adeno-associated virus type |
US6855314B1 (en) | 2000-03-22 | 2005-02-15 | The United States Of America As Represented By The Department Of Health And Human Services | AAV5 vector for transducing brain cells and lung cells |
US6468524B1 (en) | 2000-03-22 | 2002-10-22 | The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | AAV4 vector and uses thereof |
US7048920B2 (en) | 2000-03-24 | 2006-05-23 | Cell Genesys, Inc. | Recombinant oncolytic adenovirus for human melanoma |
GB0009887D0 (en) | 2000-04-20 | 2000-06-07 | Btg Int Ltd | Cytotoxic agents |
US20030013189A1 (en) | 2000-04-28 | 2003-01-16 | Wilson James M. | Compositions and methods useful for non-invasive delivery of therapeutic molecules to the bloodstream |
AU2001255575B2 (en) | 2000-04-28 | 2006-08-31 | The Trustees Of The University Of Pennsylvania | Recombinant aav vectors with aav5 capsids and aav5 vectors pseudotyped in heterologous capsids |
WO2001083797A2 (en) | 2000-04-28 | 2001-11-08 | Avigen, Inc. | Polynucleotides for use in recombinant adeno-associated virus virion production |
ATE280590T1 (de) | 2000-05-23 | 2004-11-15 | Neurologix Inc | Glutaminsäure decarboxylase (gad) abgabesystem zur behandlung neurodegeneraliver erkrankungen |
WO2001096587A2 (en) | 2000-06-13 | 2001-12-20 | The Children's Hospital Of Philadelphia | Methods for administering recombinant adeno-associated virus virions to humans previously exposed to adeno-associated virus |
DE60128916T2 (de) | 2000-07-18 | 2007-09-20 | Takeda Pharmaceutical Co. Ltd. | Neues, physiologisch aktives peptid und dessen verwendung |
US6329181B1 (en) | 2000-08-07 | 2001-12-11 | Neurologix, Inc. | Helper functions for recombinant vector production |
US6593123B1 (en) | 2000-08-07 | 2003-07-15 | Avigen, Inc. | Large-scale recombinant adeno-associated virus (rAAV) production and purification |
DE60129229T2 (de) | 2000-08-17 | 2008-05-08 | Ozawa, Keiya | Adeno-assoziierte virus-vermittelte übertragung von angiogenesefaktoren |
DE10044384A1 (de) | 2000-09-08 | 2002-04-18 | Medigene Ag | Wirtszellen zur Verpackung von rekombinantem Adeno-assoziiertem Virus (rAAV), Verfahren zu ihrer Herstellung und deren Verwendung |
FR2813891B1 (fr) | 2000-09-14 | 2005-01-14 | Immunotech Sa | Reactif multifonctionnel pour erythrocytes mettant en jeu des carbamates et applications |
GB0024550D0 (enrdf_load_stackoverflow) * | 2000-10-06 | 2000-11-22 | Oxford Biomedica Ltd | |
JP2002153278A (ja) | 2000-11-22 | 2002-05-28 | Hisamitsu Pharmaceut Co Inc | ウイルスベクターの製造に用いられる細胞、その製法およびその細胞を用いたウイルスベクターの製造方法 |
WO2002070719A2 (en) | 2001-01-19 | 2002-09-12 | Trustees Of The University Of Pennsylvania | Regulatable gene expression system |
US7588757B2 (en) | 2001-03-14 | 2009-09-15 | Genzyme Corporation | Methods of treating Parkinson's disease using recombinant adeno-associated virus virions |
CA2441454A1 (en) | 2001-03-14 | 2002-09-19 | Avigen, Inc. | Recombinant adeno-associated virus-mediated gene transfer via retroductal infusion of virions |
US6841357B1 (en) | 2001-03-30 | 2005-01-11 | Stratagene California | Method and kits for titering adeno-associated virus vectors |
US7182944B2 (en) | 2001-04-25 | 2007-02-27 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of increasing distribution of nucleic acids |
US20030096264A1 (en) | 2001-06-18 | 2003-05-22 | Psychiatric Genomics, Inc. | Multi-parameter high throughput screening assays (MPHTS) |
ES2375557T3 (es) | 2001-06-22 | 2012-03-02 | The Trustees Of The University Of Pennsylvania | Adenovirus recombinantes que comprenden prote�?nas de adenovirus de simios y usos de los mismos. |
US20040136963A1 (en) | 2001-06-22 | 2004-07-15 | The Trustees Of The University Of Pennsylvania | Simian adenovirus vectors and methods of use |
US8241622B2 (en) | 2001-07-13 | 2012-08-14 | University Of Iowa Research Foundation | Adeno-associated virus vectors with intravector heterologous terminal palindromic sequences |
EP1279740A1 (en) | 2001-07-26 | 2003-01-29 | Vrije Universiteit Brussel | Recombinant vector derived from adeno-associated virus for gene therapy |
ES2564553T3 (es) | 2001-08-08 | 2016-03-23 | The Trustees Of The University Of Pennsylvania | Procedimiento para purificar vectores víricos que tienen proteínas que se unen a ácido siálico |
US20030092161A1 (en) | 2001-09-19 | 2003-05-15 | The Trustees Of The University Of Pennsylvania | Compositions and methods for production of recombinant viruses, and uses therefor |
US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
CA2467959C (en) | 2001-11-09 | 2009-03-10 | Robert M. Kotin | Production of adeno-associated virus in insect cells |
NZ618298A (en) | 2001-11-13 | 2015-04-24 | Univ Pennsylvania | A method of detecting and/or identifying adeno-associated virus (aav) sequences and isolating novel sequences identified thereby |
CA2852277C (en) | 2001-11-21 | 2018-02-20 | Guangping Gao | Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use |
EP1944043A1 (en) | 2001-11-21 | 2008-07-16 | The Trustees of the University of Pennsylvania | Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use |
CA2469623C (en) | 2001-12-12 | 2012-05-29 | F H Faulding & Co Limited | Composition for the preservation of viruses |
ES2975413T3 (es) | 2001-12-17 | 2024-07-05 | Univ Pennsylvania | Secuencias de serotipo 8 de virus adenoasociado (AAV), vectores que las contienen y usos de las mismas |
CA2469053C (en) | 2001-12-17 | 2011-08-23 | The Trustees Of The University Of Pennsylvania | Adeno-associated virus (aav) serotype 9 sequences, vectors containing same, and uses therefor |
EP1463530A4 (en) | 2001-12-19 | 2006-09-06 | Lijun Wang | ADENO-ASSOCIATED VIRUS-RELATED DELIVERY OF GDNF TO SKELETAL MUSCLES |
WO2003062462A2 (en) | 2002-01-16 | 2003-07-31 | Dynal Biotech Asa | Method for isolating nucleic acids and protein from a single sample |
ES2411981T3 (es) | 2002-02-01 | 2013-07-09 | Oxford Biomedica (Uk) Limited | Vector lentivírico |
GB0208390D0 (en) | 2002-04-11 | 2002-05-22 | Univ London | Adeno-associated virus producer system |
US20030198620A1 (en) | 2002-04-16 | 2003-10-23 | Keiya Ozawa | Method of treating amino acid metabolic disorders using recombinant adeno-associated virus virions |
ATE348153T1 (de) | 2002-04-29 | 2007-01-15 | Univ Pennsylvania | Methode für die direkte gewinnung und amplifikation von integrierten viren aus zellulärer gewebe-dna |
DK1501921T4 (da) | 2002-04-30 | 2012-10-08 | Oncolytics Biotech Inc | Forbedrede virusrensningsmetoder |
ATE405295T1 (de) | 2002-05-01 | 2008-09-15 | Univ Florida | Verbesserte raav-expressionssysteme für die genetische modifikation spezifischer capsidproteine |
DE60335672D1 (de) | 2002-05-14 | 2011-02-17 | Merck Sharp & Dohme | Verfahren zur reinigung von adenovirus |
US7419817B2 (en) | 2002-05-17 | 2008-09-02 | The United States Of America As Represented By The Secretary Department Of Health And Human Services, Nih. | Scalable purification of AAV2, AAV4 or AAV5 using ion-exchange chromatography |
WO2003104413A2 (en) | 2002-06-05 | 2003-12-18 | University Of Florida | Production of pseudotyped recombinant aav virions |
CA2494772C (en) | 2002-08-29 | 2015-12-01 | The Board Of Trustees Of The Leland Stanford Junior University | Circular nucleic acid vectors, and methods for making and using the same |
TW200509968A (en) | 2002-11-01 | 2005-03-16 | Elan Pharm Inc | Prevention and treatment of synucleinopathic disease |
EP1418185A1 (en) | 2002-11-11 | 2004-05-12 | Aventis Pharma Deutschland GmbH | Use of EDG2 receptor in an animal model of heart failure |
US7169612B2 (en) | 2002-11-11 | 2007-01-30 | Sanofi-Aventis Deutschland Gmbh | Use of EDG2 receptor in an animal model of heart failure |
WO2004075861A2 (en) | 2003-02-26 | 2004-09-10 | Children's Hospital, Inc. | Recombinant adeno-associated virus production |
US20070172460A1 (en) | 2003-03-19 | 2007-07-26 | Jurgen Kleinschmidt | Random peptide library displayed on aav vectors |
WO2004108922A2 (en) | 2003-04-25 | 2004-12-16 | The Trustees Of The University Of Pennsylvania | Use of aav comprising a capsid protein from aav7 or aav8 for the delivery of genes encoding apoprotein a or e genes to the liver |
WO2005017101A2 (en) | 2003-05-19 | 2005-02-24 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH & HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH | Avian adenoassociated virus (aaav) and uses thereof |
DK2277996T3 (da) | 2003-05-21 | 2014-10-20 | Genzyme Corp | Fremgangsmåder til fremstilling af præparationer af rekombinante aav-virioner, der i hovedsagen er fri for tomme capsider |
EP1486567A1 (en) | 2003-06-11 | 2004-12-15 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Improved adeno-associated virus (AAV) vector for gene therapy |
JP4888876B2 (ja) | 2003-06-13 | 2012-02-29 | 田平 武 | アルツハイマー病の治療のための組換えアデノ随伴ウィルスベクター |
ES2629380T3 (es) * | 2003-06-19 | 2017-08-09 | Genzyme Corporation | Viriones de AAV con inmunorreactividad reducida y usos de los mismos |
US7291498B2 (en) | 2003-06-20 | 2007-11-06 | The Trustees Of The University Of Pennsylvania | Methods of generating chimeric adenoviruses and uses for such chimeric adenoviruses |
US7491508B2 (en) | 2003-06-20 | 2009-02-17 | The Trustees Of The University Of Pennsylvania | Methods of generating chimeric adenoviruses and uses for such chimeric adenoviruses |
US9441244B2 (en) | 2003-06-30 | 2016-09-13 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
WO2005012537A2 (en) | 2003-07-25 | 2005-02-10 | Genvec, Inc. | Adenoviral vector-based vaccines |
US7683036B2 (en) | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
WO2005030292A2 (en) | 2003-09-26 | 2005-04-07 | The Trustees Of The University Of Pennsylvania | Methods, compositions and apparatus for delivering heterologous molecules to cells |
EP2345731B1 (en) | 2003-09-30 | 2015-10-21 | The Trustees of the University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
US20060239966A1 (en) * | 2003-10-20 | 2006-10-26 | Tornoee Jens | In vivo gene therapy of parkinson's disease |
EP1742668B1 (en) | 2004-04-28 | 2011-02-09 | The Trustees of The University of Pennsylvania | Sequential delivery of immunogenic molecules via adenovirus and adeno-associated virus-mediated administrations |
WO2005116224A2 (en) * | 2004-05-18 | 2005-12-08 | Children's Memorial Hospital | Tetracycline-regulated adeno-associated viral (aav) vectors for gene delivery to the nervous system |
US7704721B2 (en) | 2004-06-01 | 2010-04-27 | Genzyme Corporation | Compositions and methods to prevent AAV vector aggregation |
CA2581714C (en) | 2004-10-05 | 2017-09-12 | Avigen, Inc. | Stepped cannula |
US7901921B2 (en) | 2004-10-22 | 2011-03-08 | Oncolytics Biotech Inc. | Viral purification methods |
CN1286981C (zh) | 2004-11-30 | 2006-11-29 | 华中科技大学同济医学院附属同济医院 | 表达人类cyp2j2反义基因的重组腺相关病毒及其制备方法 |
EP1833975A2 (en) | 2004-12-09 | 2007-09-19 | Genzyme Corporation | Regulated expression of transgenes in the central nervous system of mammals |
US8614101B2 (en) | 2008-05-20 | 2013-12-24 | Rapid Pathogen Screening, Inc. | In situ lysis of cells in lateral flow immunoassays |
US7625570B1 (en) | 2005-03-10 | 2009-12-01 | The Regents Of The University Of California | Methods for purifying adeno-associated virus |
WO2006102072A2 (en) | 2005-03-23 | 2006-09-28 | The Trustees Of The University Of Pennsylvania | Use of a pa131 polypeptide in treatment of atherosclerosis |
CN117363655A (zh) | 2005-04-07 | 2024-01-09 | 宾夕法尼亚大学托管会 | 增强腺相关病毒载体功能的方法 |
US8283151B2 (en) | 2005-04-29 | 2012-10-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Isolation, cloning and characterization of new adeno-associated virus (AAV) serotypes |
EP3520823B1 (en) | 2005-05-02 | 2021-06-30 | Genzyme Corporation | Gene therapy for neurometabolic disorders |
AU2006283189B2 (en) | 2005-08-23 | 2013-01-31 | The Regents Of The University Of California | Reflux resistant cannula and system for chronic delivery of therapeutic agents using convection-enhanced delivery |
TR201909609T4 (tr) | 2005-08-23 | 2019-07-22 | Univ Pennsylvania | Modifiye edilmiş nükleosidleri içeren rna ve kullanım yöntemleri. |
EP1857552A1 (en) | 2006-05-20 | 2007-11-21 | Cargill Incorporated | Thermostable xylose isomerase enzyme |
AU2006304997B2 (en) | 2005-10-20 | 2012-03-01 | Uniqure Ip B.V. | Improved AAV vectors produced in insect cells |
US9150882B2 (en) | 2006-01-31 | 2015-10-06 | The Board Of Trustees Of The Leland Stanford Junior University | Self-complementary parvoviral vectors, and methods for making and using the same |
WO2007120542A2 (en) * | 2006-03-30 | 2007-10-25 | The Board Of Trustees Of The Leland Stanford Junior University | Aav capsid library and aav capsid proteins |
ES2618787T5 (es) | 2006-04-25 | 2022-10-21 | Univ California | Administración de factores de crecimiento para el tratamiento de trastornos del SNC |
EP2016174A2 (en) | 2006-04-28 | 2009-01-21 | The Trustees of the University of Pennsylvania | Modified aav vectors having reduced capsid immunogenicity and use thereof |
CN101437538A (zh) | 2006-04-28 | 2009-05-20 | 宾夕法尼亚州立大学托管会 | 修饰的腺病毒六邻体蛋白和其应用 |
ES2400235T3 (es) | 2006-04-28 | 2013-04-08 | The Trustees Of The University Of Pennsylvania | Método de producción escalable de AAV |
WO2007130519A2 (en) | 2006-05-02 | 2007-11-15 | Government Of The Usa, As Represented By The Secretary, Department Of Health And Human Services | Viral nucleic acid microarray and method of use |
EP2206782A1 (en) | 2006-05-25 | 2010-07-14 | Sangamo BioSciences, Inc. | Methods and compositions for gene inactivation |
US8486635B2 (en) | 2006-05-30 | 2013-07-16 | Mayo Foundation For Medical Education And Research | Detecting and treating dementia |
MX2008015530A (es) | 2006-06-07 | 2009-02-06 | Genzyme Corp | Terapia genica para esclerosis lateral amiotrofica y otros trastornos de la medula espinal. |
EP2037892B1 (en) | 2006-06-19 | 2015-03-18 | Asklepios Biopharmaceutical, Inc. | Modified factor viii and factor ix genes and vectors for gene therapy |
EP3705577A1 (en) | 2006-06-21 | 2020-09-09 | uniQure IP B.V. | Aav vectors with improved rep coding sequences for production in insect cells |
KR20140035537A (ko) | 2006-07-21 | 2014-03-21 | 캘리포니아 인스티튜트 오브 테크놀로지 | 수지상 세포 백신접종을 위한 표적화된 유전자의 전달 |
US8945918B2 (en) | 2006-08-24 | 2015-02-03 | Virovek, Inc. | Expression in insect cells of genes with overlapping open reading frames, methods and compositions therefor |
CA2693178C (en) | 2006-11-29 | 2018-12-04 | Nationwide Children's Hospital, Inc. | Myostatin inhibition for enhancing muscle and/or improving muscle function |
NZ578816A (en) | 2007-02-02 | 2012-06-29 | Biogen Idec Inc | Use of semaphorin 6a for promoting myelination and oligodendrocyte differentiation |
US20120322861A1 (en) | 2007-02-23 | 2012-12-20 | Barry John Byrne | Compositions and Methods for Treating Diseases |
US9611302B2 (en) | 2007-04-09 | 2017-04-04 | University Of Florida Research Foundation, Inc. | High-transduction-efficiency RAAV vectors, compositions, and methods of use |
EP3492596A1 (en) | 2007-04-09 | 2019-06-05 | University of Florida Research Foundation, Inc. | Raav vector compositions having tyrosine-modified capsid proteins and methods for use |
US9725485B2 (en) | 2012-05-15 | 2017-08-08 | University Of Florida Research Foundation, Inc. | AAV vectors with high transduction efficiency and uses thereof for gene therapy |
WO2008128251A1 (en) | 2007-04-17 | 2008-10-23 | The Children's Hospital Of Philadelphia | Humanized viral vectors and methods of use thereof |
EP2012122A1 (en) | 2007-07-06 | 2009-01-07 | Medigene AG | Mutated parvovirus structural proteins as vaccines |
US20100203083A1 (en) | 2007-05-31 | 2010-08-12 | Medigene Ag | Mutated structural protein of a parvovirus |
PT2158322T (pt) | 2007-06-06 | 2017-08-09 | Genzyme Corp | Terapia genética para doenças do armazenamento lisossomal |
ATE535607T1 (de) | 2007-06-29 | 2011-12-15 | Hoffmann La Roche | Promotor |
EP2176283B1 (en) | 2007-07-14 | 2016-11-02 | University of Iowa Research Foundation | Methods and compositions for treating brain diseases |
CA2694406C (en) | 2007-07-26 | 2019-03-26 | Amsterdam Molecular Therapeutics (Amt) B.V. | Baculoviral vectors comprising repeated coding sequences with differential codon biases |
EP2198016B1 (en) | 2007-09-04 | 2015-05-27 | Her Majesty The Queen In Right of Canada as represented by The Minister of Health | Porcine adeno-associated viruses |
US9115373B2 (en) | 2007-09-19 | 2015-08-25 | Uniqure Ip B.V. | Use of AAV replication machinery for improved protein production |
EP2186283A4 (en) | 2007-10-18 | 2011-03-09 | Lg Electronics Inc | METHOD AND SYSTEM FOR TRANSMITTING AND RECEIVING SIGNALS |
US8642341B2 (en) | 2007-11-02 | 2014-02-04 | Cornell University | Materials and methods for gene mediated therapy of psychiatric disorders |
CA2707029A1 (en) | 2007-11-28 | 2009-08-27 | Soumitra Roy | Simian subfamily c adenoviruses sadv-40, -31, and -34 and uses thereof |
SG10201603993TA (en) | 2007-11-28 | 2016-07-28 | Univ Pennsylvania | SIMIAN SUBFAMILY B ADENOVIRUS SAdV-28, -27, -29, -32, -33 AND -35 AND USES THEREOF |
KR101662574B1 (ko) | 2007-11-28 | 2016-10-05 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 유인원 e 아데노바이러스 sadv-39, -25.2, -26, -30, -37, 및 -38 |
EP2247617B1 (en) | 2008-01-18 | 2013-02-27 | Genentech, Inc. | Methods and compositions for targeting polyubiquitin |
CA2713338C (en) | 2008-01-29 | 2021-10-26 | Applied Genetic Technologies Corporation | Recombinant virus production using mammalian cells in suspension |
CA2715924C (en) | 2008-02-19 | 2021-01-12 | Andrew Christian BAKKER | Optimisation of expression of parvoviral rep and cap proteins in insect cells |
CA2716928C (en) | 2008-03-04 | 2018-04-10 | The Trustees Of The University Of Pennsylvania | Simian adenoviruses sadv-36,-42.1, -42.2, and -44 and uses thereof |
WO2009120978A2 (en) | 2008-03-27 | 2009-10-01 | The Ohio State University | Treatment of metabolic-related disorders using hypothalamic gene transfer of bdnf and compositions therfor |
WO2009134681A2 (en) | 2008-04-30 | 2009-11-05 | The Trustees Of The University Of Pennsylvania | Aav7 viral vectors for targeted delivery of rpe cells |
WO2009137006A2 (en) | 2008-04-30 | 2009-11-12 | The University Of North Carolina At Chapel Hill | Directed evolution and in vivo panning of virus vectors |
MX2010012592A (es) | 2008-05-20 | 2011-05-05 | Eos Neuroscience Inc | Vectores para la administracion de proteinas sensibles a la luz y metodos de uso de las mismas. |
US9217155B2 (en) | 2008-05-28 | 2015-12-22 | University Of Massachusetts | Isolation of novel AAV'S and uses thereof |
WO2009154452A1 (en) | 2008-06-17 | 2009-12-23 | Amsterdam Molecular Therapeutics B.V. | Parvoviral capsid with incorporated Gly-Ala repeat region |
US8945885B2 (en) | 2008-07-03 | 2015-02-03 | The Board Of Trustees Of The Leland Stanford Junior University | Minicircle DNA vector preparations and methods of making and using the same |
CA2738969A1 (en) | 2008-09-29 | 2010-04-01 | Amsterdam Molecular Therapeutics (Amt) B.V. | Porphobilinogen deaminase gene therapy |
WO2010051367A1 (en) | 2008-10-31 | 2010-05-06 | The Trustees Of The University Of Pennsylvania | Simian adenoviruses sadv-43, -45,-48,-49, and -50 and uses thereof |
JP2012508591A (ja) | 2008-11-14 | 2012-04-12 | ライフ テクノロジーズ コーポレーション | 細胞を操作するための組成物および方法 |
US9415121B2 (en) | 2008-12-19 | 2016-08-16 | Nationwide Children's Hospital | Delivery of MECP2 polynucleotide using recombinant AAV9 |
EP2396343B1 (en) | 2009-02-11 | 2017-05-17 | The University of North Carolina At Chapel Hill | Modified virus vectors and methods of making and using the same |
DK2403867T3 (da) | 2009-03-04 | 2019-08-12 | Deutsches Krebsforsch | Assembly activating protein (aap) og dets anvendelse til fremstilling af parvoviruspartikler hovedsageligt bestående af vp3 |
CN102448501A (zh) | 2009-03-27 | 2012-05-09 | 西马生物医学计划公司 | 治疗肝硬化和肝纤维化的方法和组合物 |
ES2724122T3 (es) | 2009-04-30 | 2019-09-06 | Univ Pennsylvania | Composiciones para dirigir células de las vías respiratorias de conducción que comprenden construcciones de virus adenoasociado |
AU2010243489A1 (en) | 2009-05-01 | 2011-12-22 | Redbiotec Ag | Recombinant virus-like particles encoded by multi-gene vector |
FI4342992T3 (fi) | 2009-05-02 | 2025-08-12 | Genzyme Corp | Geenihoito neurodegeneratiivisiin sairauksiin |
EP2772542B1 (en) | 2009-05-28 | 2016-12-28 | Deutsches Krebsforschungszentrum | Modified AAV capsid polypeptides |
US8734809B2 (en) | 2009-05-28 | 2014-05-27 | University Of Massachusetts | AAV's and uses thereof |
EP2435559A1 (en) | 2009-05-29 | 2012-04-04 | The Trustees Of The University Of Pennsylvania | Simian adenovirus 41 and uses thereof |
PL3067417T3 (pl) | 2009-06-16 | 2019-02-28 | Genzyme Corporation | Udoskonalone sposoby oczyszczania rekombinowanych wektorów AAV |
JP2014501097A (ja) | 2009-07-06 | 2014-01-20 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 生物由来物質の産生を高めるための組成物及び方法 |
EP2292781A1 (en) | 2009-08-17 | 2011-03-09 | Genethon | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
WO2011038187A1 (en) | 2009-09-25 | 2011-03-31 | The Trustees Of The University Of Pennsylvania | Controlled adeno-associated virus (aav) diversification and libraries prepared therefrom |
CN102695526A (zh) | 2009-11-09 | 2012-09-26 | 吉恩波多治疗股份公司 | 用于神经元特异性的体内连续dopa合成的新型病毒载体构建体 |
WO2011069529A1 (en) | 2009-12-09 | 2011-06-16 | Curevac Gmbh | Mannose-containing solution for lyophilization, transfection and/or injection of nucleic acids |
ES2683695T3 (es) | 2010-01-12 | 2018-09-27 | The University Of North Carolina At Chapel Hill | Repeticiones terminales invertidas restrictivas para vectores virales |
EP2528941A4 (en) | 2010-01-25 | 2013-05-29 | Univ New York | FOR TRANSPORT STUDIES AND NEURONAL ADMINISTRATION, MANIPULATED RECOMBINANT DERIVATIVES FROM BOTULINUM NEUROTOXINES |
JP6141021B2 (ja) | 2010-02-05 | 2017-06-07 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | パルボウイルスの形質導入を増強するための組成物および方法 |
WO2011112089A2 (en) | 2010-03-11 | 2011-09-15 | Amsterdam Molecular Therapeutics (Amt) Ip B.V. | Mutated rep encoding sequences for use in aav production |
US9546112B2 (en) | 2010-03-22 | 2017-01-17 | Association Institut De Myologie | Methods of increasing efficiency of vector penetration of target tissue |
JP5922095B2 (ja) | 2010-03-29 | 2016-05-24 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 薬理学的に誘導される導入遺伝子アブレーション系 |
US9315825B2 (en) | 2010-03-29 | 2016-04-19 | The Trustees Of The University Of Pennsylvania | Pharmacologically induced transgene ablation system |
WO2011122950A1 (en) | 2010-04-01 | 2011-10-06 | Amsterdam Molecular Therapeutics (Amt) Ip B.V. | Monomeric duplex aav vectors |
JP5963743B2 (ja) * | 2010-04-23 | 2016-08-03 | ユニバーシティ オブ マサチューセッツ | Cnsターゲティングaavベクターおよびその使用方法 |
WO2011133874A1 (en) | 2010-04-23 | 2011-10-27 | University Of Massachusetts | Multicistronic expression constructs |
US9272053B2 (en) | 2010-04-23 | 2016-03-01 | University Of Massachusetts | AAV-based treatment of cholesterol-related disorders |
US8927514B2 (en) | 2010-04-30 | 2015-01-06 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
US9839696B2 (en) | 2010-04-30 | 2017-12-12 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
US9309534B2 (en) * | 2010-07-12 | 2016-04-12 | Universidad Autonoma De Barcelona | Gene therapy composition for use in diabetes treatment |
US8808684B2 (en) | 2010-09-10 | 2014-08-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Epidermal growth factor receptor (EGFR) and methods of use in adenoviral-associated virus type 6 (AAV6) transduction |
WO2012046727A1 (ja) | 2010-10-05 | 2012-04-12 | タカラバイオ株式会社 | ウイルスベクターの製造方法 |
US8663624B2 (en) | 2010-10-06 | 2014-03-04 | The Regents Of The University Of California | Adeno-associated virus virions with variant capsid and methods of use thereof |
WO2012051343A1 (en) | 2010-10-12 | 2012-04-19 | The Children's Hospital Of Philadelphia | Methods and compositions for treating hemophilia b |
CN107828820B (zh) * | 2010-10-27 | 2022-06-07 | 学校法人自治医科大学 | 用于向神经系统细胞导入基因的腺相关病毒粒子 |
EP2635906A4 (en) | 2010-11-05 | 2014-04-02 | Univ Brandeis | Ice inhibiting compounds and uses thereof |
WO2012064920A1 (en) | 2010-11-11 | 2012-05-18 | University Of Miami | Methods, compositions, cells, and kits for treating ischemic injury |
WO2012071318A2 (en) | 2010-11-23 | 2012-05-31 | The Trustees Of The University Of Pennsylvania | Subfamily e simian adenoviruses a1321, a1325, a1295, a1309, a1316 and a1322 and uses thereof |
EP4234571A3 (en) | 2011-02-10 | 2023-09-27 | The University of North Carolina at Chapel Hill | Viral vectors with modified transduction profiles and methods of making and using the same |
TR201908020T4 (tr) | 2011-02-17 | 2019-06-21 | Univ Pennsylvania | Doku özgüllüğünü değiştirmek ve aav9-aracılı gen transferini geliştirmek için bileşimler ve yöntemler. |
BR112013021494B1 (pt) * | 2011-02-22 | 2021-09-08 | California Institute Of Technology | Vetor viral, polinucleotídeo isolado, uso de um vírus adeno-associado (aav) recombinante e método para produzir o mesmo |
GB201103062D0 (en) | 2011-02-22 | 2011-04-06 | Isis Innovation | Method |
US20120220648A1 (en) * | 2011-02-24 | 2012-08-30 | National Taiwan University Hospital | Method of Treating Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency Using Adeno-Associated Virus (AAV)-AADC Vector |
EP2500434A1 (en) | 2011-03-12 | 2012-09-19 | Association Institut de Myologie | Capsid-free AAV vectors, compositions, and methods for vector production and gene delivery |
EP3777843B1 (en) | 2011-04-18 | 2023-01-04 | National Center of Neurology and Psychiatry | Drug delivery particle and method for producing the same |
EP3699286A1 (en) | 2011-04-20 | 2020-08-26 | The Trustees of the University of Pennsylvania | Regimens and compositions for aav-mediated passive immunization of airborne pathogens |
CA2870511C (en) | 2011-04-21 | 2023-08-08 | University Of Massachusetts | Raav-based compositions and methods for treating alpha-1 anti-trypsin deficiencies |
KR102121355B1 (ko) | 2011-04-22 | 2020-06-11 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 변이체 캡시드를 지니는 아데노-관련 바이러스 및 이의 사용 방법 |
US9249425B2 (en) | 2011-05-16 | 2016-02-02 | The Trustees Of The University Of Pennslyvania | Proviral plasmids and production of recombinant adeno-associated virus |
US9598468B2 (en) | 2011-05-18 | 2017-03-21 | University Of Florida Research Foundation, Incorporated | Polypeptides and vectors for targeting HER2/neu expressing cells and uses thereof |
US20120295960A1 (en) * | 2011-05-20 | 2012-11-22 | Oxford Biomedica (Uk) Ltd. | Treatment regimen for parkinson's disease |
JP6153516B2 (ja) | 2011-06-06 | 2017-06-28 | バイオカーティス エヌベー | イオン性界面活性剤による細胞の選択的溶解 |
BR112014001863A2 (pt) | 2011-07-27 | 2017-02-21 | Genethon | sistemas de expressão baculovírus melhorados |
DK2744895T3 (en) | 2011-09-08 | 2016-01-04 | Uniqure Ip Bv | REMOVAL OF INFECTED VIRA FROM AAV PREPARATIONS |
WO2013036889A1 (en) | 2011-09-09 | 2013-03-14 | University Of Washington | Retrograde transport peptide and use of same for delivery to central nervous system |
JP6165752B2 (ja) | 2011-10-28 | 2017-07-19 | ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | アデノ随伴ウイルスの産生のための細胞株 |
GB201118636D0 (en) | 2011-10-28 | 2011-12-07 | Oxford Biomedica Ltd | Nucleotide sequence |
AU2012340567B2 (en) | 2011-11-22 | 2017-11-23 | The Children's Hospital Of Philadelphia | Virus vectors for highly efficient transgene delivery |
WO2013078199A2 (en) | 2011-11-23 | 2013-05-30 | Children's Medical Center Corporation | Methods for enhanced in vivo delivery of synthetic, modified rnas |
WO2013078316A1 (en) | 2011-11-23 | 2013-05-30 | Nationwide Children's Hospital, Inc. | Recombinant adeno-associated virus delivery of alpha-sarcoglycan polynucleotides |
WO2013103896A1 (en) | 2012-01-06 | 2013-07-11 | Mayo Foundation For Medical Education And Research | Treating cardiovascular or renal diseases |
JP6562632B2 (ja) | 2012-02-14 | 2019-08-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 心血管疾患および他の状態のためのパラクリン遺伝子の全身送達および制御された発現 |
BR112014020325A2 (pt) | 2012-02-17 | 2017-08-08 | Childrens Hospital Philadelphia | composições de vetor do aav e métodos para a transferência de gene para as células, órgãos e tecidos |
PL2839014T3 (pl) | 2012-04-18 | 2021-08-23 | The Children's Hospital Of Philadelphia | Kompozycja i sposoby na wysoko wydajny transfer genu za pomocą kapsydu wariantów aav |
EP2660325A3 (en) | 2012-05-02 | 2014-02-12 | Christian Medical College | AAV vectors and corresponding nucleotide sequences and methods |
US9163259B2 (en) | 2012-05-04 | 2015-10-20 | Novartis Ag | Viral vectors for the treatment of retinal dystrophy |
CA2871920C (en) | 2012-05-08 | 2021-03-09 | Merck Sharp & Dohme Corp. | Permeable glycosidase inhibitors and uses thereof |
JP6385920B2 (ja) | 2012-05-09 | 2018-09-05 | オレゴン ヘルス アンド サイエンス ユニバーシティー | アデノ随伴ウイルスプラスミド及びベクター |
TWI775096B (zh) | 2012-05-15 | 2022-08-21 | 澳大利亞商艾佛蘭屈澳洲私營有限公司 | 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd) |
US10294281B2 (en) | 2012-05-15 | 2019-05-21 | University Of Florida Research Foundation, Incorporated | High-transduction-efficiency rAAV vectors, compositions, and methods of use |
CN105473723A (zh) | 2012-05-18 | 2016-04-06 | 宾夕法尼亚大学托管会 | 亚家族e猿腺病毒a1302、a1320、a1331和a1337及其用途 |
KR101738438B1 (ko) | 2012-07-06 | 2017-05-22 | 다카라 바이오 가부시키가이샤 | 아데노-관련 바이러스 벡터의 생산세포 |
IN2015KN00074A (enrdf_load_stackoverflow) | 2012-07-06 | 2015-07-31 | Univ Iowa Res Found | |
BR112015002168A2 (pt) | 2012-08-01 | 2017-11-07 | Nationwide Childrens Hospital | liberação intratecal de vírus 9 adeno-associado recombinante |
US10166299B2 (en) | 2012-08-31 | 2019-01-01 | The United States Of America As Represented By The Secretary Dept. Of Health And Human Services National Institutes Of Health | AAV mediated aquaporin gene transfer to treat Sjogren's syndrome |
US9636370B2 (en) | 2012-09-28 | 2017-05-02 | The University Of North Carolina At Chapel Hill | AAV vectors targeted to oligodendrocytes |
WO2014071042A1 (en) | 2012-10-31 | 2014-05-08 | The Trustees Of Columbia University In The City Of New York | Methods for identifying candidates for the treatment of neurodegenerative diseases |
SG11201504523UA (en) | 2012-12-12 | 2015-07-30 | Broad Inst Inc | Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications |
US9938541B2 (en) | 2012-12-25 | 2018-04-10 | Takara Bio Inc. | AAV variant |
HUE037482T2 (hu) | 2013-01-08 | 2018-08-28 | Genzyme Corp | Inos-inhibitorok alkalmazása vírushozam növelésére tenyészetben |
US9066966B2 (en) | 2013-02-01 | 2015-06-30 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Methods and pharmaceutical compositions for the treatment of cardiomyopathy due to friedreich ataxia |
ES2741502T3 (es) | 2013-02-08 | 2020-02-11 | Univ Pennsylvania | Cápside de AAV8 modificada para la transferencia génica para terapias de retina |
CA2905952A1 (en) | 2013-03-13 | 2014-10-02 | The Children's Hospital Of Philadelphia | Adeno-associated virus vectors and methods of use thereof |
EP2970943A4 (en) | 2013-03-15 | 2017-04-19 | The Children's Hospital of Philadelphia | Vectors comprising stuffer/filler polynucleotide sequences and methods of use |
EP2970966A4 (en) | 2013-03-15 | 2016-10-26 | Univ North Carolina | SYNTHETIC ADENOASSOZED VIRUS INVERTED REPEAT SEQUENCES |
CA2909085C (en) | 2013-04-08 | 2023-08-29 | University Of Iowa Research Foundation | Chimeric adeno-associated virus/ bocavirus parvovirus vector |
EP2792742A1 (en) | 2013-04-17 | 2014-10-22 | Universitätsklinikum Hamburg-Eppendorf (UKE) | Gene-therapy vectors for treating cardiomyopathy |
USRE50283E1 (en) | 2013-04-18 | 2025-01-28 | Fondazione Telethon Ets | Effective delivery of large genes by dual AAV vectors |
CN105324392A (zh) | 2013-04-20 | 2016-02-10 | 全国儿童医院研究所 | 外显子2靶向U7snRNA多核苷酸构建体的重组腺相关病毒递送 |
WO2015012924A2 (en) | 2013-04-29 | 2015-01-29 | The Trustees Of The University Of Pennsylvania | Tissue preferential codon modified expression cassettes, vectors containing same, and use thereof |
CN115120746A (zh) | 2013-05-15 | 2022-09-30 | 明尼苏达大学董事会 | 腺相关病毒介导的基因向中枢神经系统转移 |
WO2014186746A1 (en) | 2013-05-16 | 2014-11-20 | University Of Florida Research Foundation, Inc. | HAIRPIN mRNA ELEMENTS AND METHODS FOR THE REGULATION OF PROTEIN TRANSLATION |
CA2907799A1 (en) | 2013-05-31 | 2014-12-04 | The Regents Of The University Of California | Adeno-associated virus variants and methods of use thereof |
WO2014201308A1 (en) | 2013-06-12 | 2014-12-18 | Washington University | Endothelial-targeted adenoviral vectors, methods and uses therefor |
EP3008191A2 (en) | 2013-06-13 | 2016-04-20 | Shire Human Genetic Therapies, Inc. | Messenger rna based viral production |
US9840719B2 (en) | 2013-07-22 | 2017-12-12 | The Children's Hospital Of Philadelphia | Variant AAV and compositions, methods and uses for gene transfer to cells, organs and tissues |
JP6752142B2 (ja) | 2013-07-26 | 2020-09-09 | ユニバーシティー オブ アイオワ リサーチ ファウンデーション | 脳疾患を処置するための方法および組成物 |
ITTO20130669A1 (it) | 2013-08-05 | 2015-02-06 | Consiglio Nazionale Ricerche | Vettore adeno-associato ricombinante muscolo-specifico e suo impiego nel trattamento di patologie muscolari |
WO2015031686A1 (en) | 2013-08-30 | 2015-03-05 | Amgen Inc. | High titer recombinant aav vector production in adherent and suspension cells |
AU2014318890B2 (en) | 2013-09-12 | 2019-03-07 | Biomarin Pharmaceutical Inc. | Adeno-associated virus Factor VIII vectors |
US9585971B2 (en) | 2013-09-13 | 2017-03-07 | California Institute Of Technology | Recombinant AAV capsid protein |
US20160369298A1 (en) | 2013-09-26 | 2016-12-22 | University Of Florida Research Foundation, Inc. | Synthetic combinatorial aav capsid library for targeted gene therapy |
EP3068889B1 (en) | 2013-09-26 | 2019-04-17 | Universitat Autònoma De Barcelona | Gene therapy compositions for use in the prevention and/or treatment of non-alcoholic fatty liver disease |
ES2714535T3 (es) | 2013-10-11 | 2019-05-28 | Massachusetts Eye & Ear Infirmary | Métodos para predecir secuencias de virus ancestrales y usos de los mismos |
CA2927366A1 (en) | 2013-10-24 | 2015-04-30 | Uniqure Ip B.V. | Aav-5 pseudotyped vector for gene therapy for neurological diseases |
US20160272687A1 (en) | 2013-11-08 | 2016-09-22 | The Board Of Trustees Of The University Of Arkansas | Adeno-associated virus "x" oncogene |
MX375360B (es) | 2013-11-26 | 2025-03-06 | Us Health | Vectores de virus adeno-asociado para el tratamiento de la enfermedad de almacenamiento de glucógeno. |
WO2015080223A1 (ja) | 2013-11-29 | 2015-06-04 | タカラバイオ株式会社 | アデノ随伴ウイルスの定量方法 |
EP3572513A1 (en) | 2013-12-09 | 2019-11-27 | Baylor College of Medicine | Hippo and dystrophin complex signaling in cardiomyocyte renewal |
AU2014362248A1 (en) | 2013-12-12 | 2016-06-16 | Massachusetts Institute Of Technology | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
GB201322798D0 (en) | 2013-12-20 | 2014-02-05 | Oxford Biomedica Ltd | Production system |
ES2732208T3 (es) | 2014-01-09 | 2019-11-21 | Genethon | Métodos para el diagnóstico o el seguimiento de distrofias musculares |
WO2015106273A2 (en) | 2014-01-13 | 2015-07-16 | Trustees Of Boston University | Methods and assays relating to huntingtons disease and parkinson's disease |
GB201401707D0 (en) | 2014-01-31 | 2014-03-19 | Sec Dep For Health The | Adeno-associated viral vectors |
GB201403684D0 (en) | 2014-03-03 | 2014-04-16 | King S College London | Vector |
BR112016016274A2 (pt) | 2014-02-19 | 2017-10-03 | Hoffmann La Roche | Ponte da barreira hematoencefálica |
WO2015124546A1 (en) | 2014-02-19 | 2015-08-27 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii- Cnic | Aav vectors for the treatment of ischemic and non-ischemic heart disease |
US10072251B2 (en) | 2014-02-19 | 2018-09-11 | University Of Massachusetts | Recombinant AAVS having useful transcytosis properties |
WO2015126972A1 (en) | 2014-02-21 | 2015-08-27 | University Of Florida Research Foundation, Inc. | Methods and compositions for gene delivery to on bipolar cells |
EP3450571B1 (en) | 2014-02-24 | 2023-04-05 | Celgene Corporation | Methods of using an activator of cereblon for neural cell expansion and the treatment of central nervous system disorders |
WO2015131076A1 (en) | 2014-02-27 | 2015-09-03 | Yale University | Nlrp6 inflammasome intestinal epithelium mucus secretion |
US10308957B2 (en) | 2014-03-04 | 2019-06-04 | University Of Florida Research Foundation, Inc. | rAAV vectors and methods for transduction of photoreceptors and RPE cells |
MX2016011517A (es) | 2014-03-07 | 2017-04-13 | Univ Arizona | Peptidos de crmp2 no narcoticos que seleccionan como diana canales de sodio para el dolor cronico. |
HRP20201544T1 (hr) | 2014-03-09 | 2021-02-19 | The Trustees Of The University Of Pennsylvania | Pripravci korisni u liječenju nedostatka ornitinske transkarbamilaze (otc) |
WO2015137802A1 (en) | 2014-03-10 | 2015-09-17 | Uniqure Ip B.V. | Further improved aav vectors produced in insect cells |
WO2015152813A1 (en) | 2014-04-03 | 2015-10-08 | Deniz Kirik | Gene expression system and regulation thereof |
WO2015157070A2 (en) | 2014-04-09 | 2015-10-15 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating cystic fibrosis |
EP2933335A1 (en) | 2014-04-18 | 2015-10-21 | Genethon | A method of treating peripheral neuropathies and motor neuron diseases |
US10975391B2 (en) | 2014-04-25 | 2021-04-13 | University Of Massachusetts | Recombinant AAV vectors useful for reducing immunity against transgene products |
ES2876409T3 (es) | 2014-04-25 | 2021-11-12 | Univ Pennsylvania | Variantes del RLBD y su uso en composiciones para reducir los niveles de colesterol |
US20170088819A1 (en) | 2014-05-16 | 2017-03-30 | Vrije Universiteit Brussel | Genetic correction of myotonic dystrophy type 1 |
WO2015191508A1 (en) | 2014-06-09 | 2015-12-17 | Voyager Therapeutics, Inc. | Chimeric capsids |
EP3154560B1 (en) | 2014-06-13 | 2019-03-13 | University of Pittsburgh - Of the Commonwealth System of Higher Education | Methods and materials for increasing viral vector infectivity |
WO2015196179A1 (en) | 2014-06-20 | 2015-12-23 | University Of Florida Research Foundation, Inc. | Methods of packaging multiple adeno-associated virus vectors |
EP2960336A1 (en) | 2014-06-27 | 2015-12-30 | Genethon | Efficient systemic treatment of dystrophic muscle pathologies |
WO2016004319A1 (en) | 2014-07-02 | 2016-01-07 | University Of Florida Research Foundation, Inc. | Compositions and methods for purifying recombinant adeno-associated virus |
US10023846B2 (en) | 2014-07-10 | 2018-07-17 | Takara Bio Inc. | Production method for non-enveloped virus particles |
US9616090B2 (en) | 2014-07-30 | 2017-04-11 | Sangamo Biosciences, Inc. | Gene correction of SCID-related genes in hematopoietic stem and progenitor cells |
US10392622B2 (en) | 2014-08-01 | 2019-08-27 | The Trustees Of The University Of Pennsylvania | Compositions and methods for self-regulated inducible gene expression |
WO2016054557A1 (en) | 2014-10-03 | 2016-04-07 | University Of Massachusetts | Novel high efficiency library-identified aav vectors |
WO2016054554A1 (en) | 2014-10-03 | 2016-04-07 | University Of Massachusetts | Heterologous targeting peptide grafted aavs |
US10842886B2 (en) | 2014-10-10 | 2020-11-24 | Research Institute At Nationwide Children's Hospital | Guided injections for AAV gene transfer to muscle |
WO2016065001A1 (en) | 2014-10-21 | 2016-04-28 | University Of Massachusetts | Recombinant aav variants and uses thereof |
JP6401871B2 (ja) | 2014-11-05 | 2018-10-10 | ボイジャー セラピューティクス インコーポレイテッドVoyager Therapeutics,Inc. | パーキンソン病の治療のためのaadcポリヌクレオチド |
EP3690024A1 (en) | 2014-11-05 | 2020-08-05 | The Research Institute at Nationwide Children's Hospital | Methods and materials for producing recombinant viruses in eukaryotic microalgae |
SG11201703237VA (en) | 2014-11-19 | 2017-06-29 | Axon Neuroscience Se | Humanized tau antibodies in alzheimer's disease |
CN107532173A (zh) | 2014-11-21 | 2018-01-02 | 北卡罗来纳-查佩尔山大学 | 靶向中枢神经系统的aav载体 |
WO2016081927A2 (en) | 2014-11-21 | 2016-05-26 | University Of Florida Research Foundation, Inc. | Genome-modified recombinant adeno-associated virus vectors |
CN107208142B (zh) | 2014-11-28 | 2024-03-26 | 优尼科Ip有限公司 | 包含细小病毒病毒体的组合物中的dna杂质 |
US11697825B2 (en) | 2014-12-12 | 2023-07-11 | Voyager Therapeutics, Inc. | Compositions and methods for the production of scAAV |
CA2972807C (en) | 2015-01-14 | 2024-01-16 | The University Of North Carolina At Chapel Hill | Methods and compositions for targeted gene transfer |
JP2018506530A (ja) | 2015-01-30 | 2018-03-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 脊柱軟膜下遺伝子送達システム |
US20180030096A1 (en) | 2015-02-03 | 2018-02-01 | University Of Florida Research Foundation, Inc. | Recombinant aav1, aav5, and aav6 capsid mutants and uses thereof |
KR102625784B1 (ko) | 2015-02-10 | 2024-01-15 | 젠자임 코포레이션 | 선조체 및 피질로의 바이러스 입자의 향상된 전달 |
US20180245073A1 (en) | 2015-02-23 | 2018-08-30 | Voyager Therapeutics, Inc. | Regulatable expression using adeno-associated virus (aav) |
EP3268024B1 (en) | 2015-03-10 | 2020-09-09 | The Trustees of Columbia University in the City of New York | Recombinant glut1 adeno-associated viral vector constructs and related methods for restoring glut1 expression |
US20180094280A1 (en) | 2015-03-20 | 2018-04-05 | Bluebird Bio, Inc. | Vector formulations |
MX388331B (es) | 2015-03-24 | 2025-03-19 | Univ California | Variantes de virus adenoasociado y métodos de uso de estas |
JP6892433B2 (ja) | 2015-04-03 | 2021-06-23 | ユニバーシティ・オブ・マサチューセッツUniversity Of Massachusetts | 十分に安定化された非対称sirna |
US10081659B2 (en) | 2015-04-06 | 2018-09-25 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Adeno-associated vectors for enhanced transduction and reduced immunogenicity |
TWI707951B (zh) | 2015-04-08 | 2020-10-21 | 美商健臻公司 | 過大腺相關載體之製造 |
CN115074366A (zh) | 2015-04-16 | 2022-09-20 | 埃默里大学 | 用于肝脏中蛋白质表达的重组启动子和载体及其用途 |
EP4491733A3 (en) | 2015-04-23 | 2025-03-26 | University of Massachusetts | Modulation of aav vector transgene expression |
WO2016172008A1 (en) | 2015-04-24 | 2016-10-27 | University Of Massachusetts | Modified aav constructions and uses thereof |
US20160346359A1 (en) | 2015-05-01 | 2016-12-01 | Spark Therapeutics, Inc. | Adeno-associated Virus-Mediated CRISPR-Cas9 Treatment of Ocular Disease |
AU2016256894B2 (en) | 2015-05-07 | 2020-11-26 | Massachusetts Eye And Ear Infirmary | Methods of delivering an agent to the eye |
US9682193B2 (en) | 2015-05-11 | 2017-06-20 | Alcyone Lifesciences, Inc. | Drug delivery systems and methods |
CA2985786A1 (en) | 2015-05-12 | 2016-11-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Aav isolate and fusion protein comprising nerve growth factor signal peptide and parathyroid hormone |
US20170067028A1 (en) | 2015-05-15 | 2017-03-09 | Douglas J. Ballon | Radiolabeling of adeno associated virus |
US10729790B2 (en) | 2015-05-26 | 2020-08-04 | Salk Institute For Biological Studies | Motor neuron-specific expression vectors |
IL283475B2 (en) | 2015-05-28 | 2024-07-01 | Univ Cornell | Adeno-associated virus mediated delivery of c1ei as a therapy for angioedema |
WO2016196507A1 (en) | 2015-05-29 | 2016-12-08 | University Of Iowa Research Foundation | Methods of delivery of transgenes for treating brain diseases |
RU2021134920A (ru) | 2015-05-29 | 2022-04-15 | Дзе Трастиз Оф Дзе Юнивёрсити Оф Пенсильвания | Композиции и способы деградации неправильно упакованных белков |
DK3313991T3 (da) | 2015-06-23 | 2024-09-09 | Childrens Hospital Philadelphia | Modificeret faktor ix og sammensætninger, fremgangsmåder og anvendelser til genoverførsel til celler, organer og væv |
US11266748B2 (en) | 2015-07-02 | 2022-03-08 | University Of Florida Research Foundation, Incorporated | Recombinant adeno-associated virus vectors to target medullary thyroid carcinoma |
EP3320101B1 (en) | 2015-07-07 | 2021-08-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for expressing a polynucleotide of interest in the peripheral nervous system of a subject |
US20170007669A1 (en) | 2015-07-07 | 2017-01-12 | Mayo Foundation For Medical Education And Research | Peptide-mediated delivery of active agents across the blood-brain barrier |
WO2017015102A1 (en) | 2015-07-17 | 2017-01-26 | The Trustees Of The University Of Pennsylvania | Compositions and methods for achieving high levels of transduction in human liver cells |
US20180214576A1 (en) | 2015-07-28 | 2018-08-02 | University Of Massachusetts | Transgenic expression of dnasei in vivo delivered by an adeno-associated virus vector |
US10738087B2 (en) | 2015-07-30 | 2020-08-11 | Massachusetts Eye And Ear Infirmary | Ancestral virus sequences and uses thereof |
US20190000940A1 (en) | 2015-07-31 | 2019-01-03 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of aadc deficiency |
KR102745604B1 (ko) | 2015-08-06 | 2024-12-23 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | Glp-1 및 대사성 질환 치료용 조성물에서 이의 용도 |
WO2017053677A1 (en) | 2015-09-24 | 2017-03-30 | Biomarin Pharmaceutical Inc. | Adeno-associated virus factor viii vectors, associated viral particles and therapeutic formulations comprising the same |
CN108137655B (zh) | 2015-09-28 | 2022-04-22 | 北卡罗来纳-查佩尔山大学 | 逃避抗体的病毒载体的方法和组合物 |
PL3359666T3 (pl) | 2015-10-09 | 2025-06-23 | Genzyme Corporation | Wczesna izolacja komórek po transfekcji (epic) do wytwarzania środków biologicznych |
US10123969B2 (en) | 2015-10-15 | 2018-11-13 | Wisconsin Alumni Research Foundation | Osmotic enhancement of drug/therapeutic delivery to the brain following infusion or injection into the cerebrospinal fluid |
US12188037B2 (en) | 2015-10-22 | 2025-01-07 | University Of Florida Research Foundation, Incorporated | Synthetic combinatorial AAV3 capsid library |
EP3364997B1 (en) | 2015-10-22 | 2024-01-17 | University of Massachusetts | Aspartoacylase gene therapy in the treatment of canavan disease |
EP3364996B1 (en) | 2015-10-22 | 2021-08-25 | University of Massachusetts | Prostate-targeting adeno-associated virus serotype vectors |
AU2016341428B2 (en) | 2015-10-23 | 2021-12-02 | University Of Iowa Research Foundation | Methods for treating neurodegenerative diseases using gene therapy to delay disease onset and progression while providing cognitive protection |
WO2017075335A1 (en) | 2015-10-28 | 2017-05-04 | Voyager Therapeutics, Inc. | Regulatable expression using adeno-associated virus (aav) |
EP3368563A1 (en) | 2015-10-28 | 2018-09-05 | The Trustees Of The University Of Pennsylvania | Intrathecal administration of adeno-associated-viral vectors for gene therapy |
CN108602884B (zh) | 2015-11-08 | 2024-06-25 | 豪夫迈·罗氏有限公司 | 筛选多特异性抗体的方法 |
US10633662B2 (en) | 2015-11-10 | 2020-04-28 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for modulating AAV infection |
CO2018006699A2 (es) | 2015-12-01 | 2018-09-20 | Spark Therapeutics Inc | Métodos escalables para producir un vector viral adenoasociado (aav) recombinante en un sistema de cultivo celular en suspensión sin suero adecuado para uso clínico |
US20170151416A1 (en) | 2015-12-01 | 2017-06-01 | Invivo Therapeutics Corporation | Methods and Systems for Delivery of a Trail of a Therapeutic Substance into an Anatomical Space |
EP3384034B1 (en) | 2015-12-02 | 2020-07-08 | The Board of Trustees of the Leland Stanford Junior University | Novel recombinant adeno-associated virus capsids with enhanced human skeletal muscle tropism |
US10406244B2 (en) | 2015-12-02 | 2019-09-10 | The Board Of Trustees Of The Leland Stanford Junior University | AAV vectors with expanded packaging capacity |
EP3383896A1 (en) | 2015-12-03 | 2018-10-10 | Genethon | Compositions and methods for improving viral vector efficiency |
WO2017160360A2 (en) | 2015-12-11 | 2017-09-21 | The Trustees Of The University Of Pennsylvania | Scalable purification method for aav9 |
US11015174B2 (en) | 2015-12-11 | 2021-05-25 | The Trustees Of The University Of Pennsylvania | Scalable purification method for AAV8 |
US11015173B2 (en) | 2015-12-11 | 2021-05-25 | The Trustees Of The University Of Pennsylvania | Scalable purification method for AAV1 |
IL259842B (en) | 2015-12-11 | 2022-08-01 | California Inst Of Techn | Targeting peptides for directing adeno-associated viruses -aavs- |
ES2918998T3 (es) | 2015-12-11 | 2022-07-21 | Univ Pennsylvania | Método de purificación escalable para AAVrh10 |
MX395524B (es) | 2015-12-14 | 2025-03-25 | Univ North Carolina Chapel Hill | Proteinas de cápside modificadas para un suministro mejorado de vectores de parvovirus. |
US11208630B2 (en) | 2015-12-24 | 2021-12-28 | University Of Florida Research Foundation, Incorporated | AAV production using suspension adapted cells |
EP3769788A1 (en) | 2016-01-13 | 2021-01-27 | Genzyme Corporation | Recombinant aav vectors expressing osteoprotective genes, including has2 and lubricin, useful in the treatment of osteoarthritis and related joint conditions in mammals |
US20190022251A1 (en) | 2016-01-15 | 2019-01-24 | Jichi Medical University | Adeno-Associated Virus Virions for Treatment of Epilepsy |
EP3411059A4 (en) | 2016-02-02 | 2019-10-16 | University Of Massachusetts | METHOD FOR INCREASING THE EFFECTIVENESS OF THE SYSTEMIC DELIVERY OF AVV GENES TO THE CENTRAL NERVOUS SYSTEM |
JP2019504888A (ja) | 2016-02-05 | 2019-02-21 | エモリー ユニバーシティ | 一本鎖アデノ随伴ウイルス9または自己相補型アデノ随伴ウイルス9の脳脊髄液への注射 |
US11702672B2 (en) | 2016-02-08 | 2023-07-18 | University Of Iowa Research Foundation | Methods to produce chimeric adeno-associated virus/bocavirus parvovirus |
AU2017219865B2 (en) | 2016-02-16 | 2023-04-13 | The Board Of Trustees Of The Leland Stanford Junior University | Novel recombinant adeno-associated virus capsids resistant to pre-existing human neutralizing antibodies |
US20190071681A1 (en) | 2016-02-26 | 2019-03-07 | University Of Florida Research Foundation, Incorporated | Aav heparin mutants that display significantly improved eye and brain transduction |
WO2017151884A1 (en) | 2016-03-02 | 2017-09-08 | The Children's Hospital Of Philadelphia | Therapy for frontotemporal dementia |
LT3423110T (lt) | 2016-03-03 | 2021-12-27 | University Of Massachusetts | Linijinis dnr dupleksas su uždarais galais, skirtas nevirusiniam geno pernešimui |
AU2017229347A1 (en) | 2016-03-07 | 2018-11-01 | University Of Iowa Research Foundation | AAV-mediated expression using a synthetic promoter and enhancer |
EP3433266B1 (en) | 2016-03-23 | 2025-07-02 | The Regents of the University of California | Methods of treating mitochondrial disorders |
WO2017165859A1 (en) | 2016-03-24 | 2017-09-28 | Research Institute At Nationwide Children's Hospital | Modified viral capsid proteins |
CA3018380A1 (en) | 2016-03-28 | 2017-10-05 | Dimension Therapeutics, Inc. | Methods of heat inactivation of adenovirus |
AU2017245099B2 (en) | 2016-03-28 | 2021-07-29 | The Regents Of The University Of California | Anti-Ryk antibodies and methods of using the same |
EP3436576A4 (en) | 2016-03-30 | 2019-10-30 | Spark Therapeutics, Inc. | CELL LINE FOR RECOMBINANT PROTEIN AND / OR VIRUS VECTOR PRODUCTION |
AU2017240721B2 (en) | 2016-03-31 | 2023-10-12 | Spark Therapeutics, Inc. | Column-based fully scalable rAAV manufacturing process |
EP3443108A4 (en) | 2016-04-15 | 2019-11-20 | The Trustees of The University of Pennsylvania | NOVEL AAV8 MUTANT CAPSIDES AND COMPOSITIONS THEREOF |
KR20250065734A (ko) | 2016-04-16 | 2025-05-13 | 유니버시티 오브 플로리다 리서치 파운데이션, 인코포레이티드 | 바큘로바이러스 시스템-생산된 재조합 아데노-연관 바이러스의 생물학적 효력을 증진시키는 방법 |
KR20180134846A (ko) | 2016-04-21 | 2018-12-19 | 바이로베크 인코포레이티드 | 곤충 세포에서의 aav 생산, 및 이를 위한 방법 및 조성물 |
EP3235516B1 (en) | 2016-04-22 | 2019-06-26 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts Universitätsmedizin | Regulatable adeno-associated virus (aav) vector |
EP3449250B1 (en) | 2016-04-28 | 2020-11-04 | Indiana University Research & Technology Corporation | Methods and compositions for resolving components of a virus preparation |
WO2017192699A1 (en) | 2016-05-03 | 2017-11-09 | Children's Medical Research Institute | Adeno-associated virus polynucleotides, polypeptides and virions |
US11866462B2 (en) | 2016-05-04 | 2024-01-09 | Oregon Health & Science University | Recombinant adeno-associated viral vectors |
WO2018191450A2 (en) | 2017-04-14 | 2018-10-18 | National Taiwan University Hospital | Gene therapy for aadc deficiency |
JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
AU2019268330A1 (en) | 2018-05-15 | 2020-11-26 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of Parkinson's disease |
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